PROCESS TO PREPARE HERBICIDAL BICYCLIC TRIAZOLES

Abstract: This invention pertains to a process to prepare Formula (I) compounds, wherein Q and Z are defined within. This invention also pertains to intermediates of Formula (II) and (IV), wherein Q, X, Z and R<2> are defined within.

Description: TITLE PROCESS TO PREPARE HERBICIDAL BICYCUC TRIAZOLES BACKGROUND OF THE INNENTION U.S. 4,925,481, U.S. 4,213,773 and U.S. 4,881,967 disclose herbicidal tetrahydrotriazolopyridin-3-ones and methods for preparation, but do not disclose the instant process. SUMMARY OF THE INVENTION The invention pertains to a process to prepare compounds of Formula I wherein Q is Q-l Q-2 Q-3 Q-4 R 1 is H, halogen, OH, C r C 6 alkyl, C C 6 haloalkyl, C C 6 alkoxy, C r C 6 haloalkoxy, C j -Cg alkylthio, Cj-Cg haloalkylthio, C 2 -C 6 alkenyloxy, C 2 -C 6 alkenylthio, C 2 -C 6 haloalkenyloxy, C 2 -Cg haloalkenylthio, C3-C6 alkynyloxy, C^- 6 alkynylthio, C3-C 6 haloalkynyloxy, C3-C6 haloalkynylthio, C 2 -C< $ alkylcarbonyl, C 2 -Cg alkoxycarbonyl, C 4 -Cg alkenyloxycarbonyl, C3-C alkylcarbonylalkoxy, C3-C8 alkylcarbonyl- alkylthio, C3-C8 alkoxycarbonylalkoxy, C3-C8 alkoxycarbonyl- alkylthio, C 5 -Cg alkenyloxycarbonylalkoxy, C 5 -Cg alkenyloxycarbonyl- alkylthio, phenoxy and phenylthio where the phenyl groups are optionally substituted with halogen; R 3 is H, C r C 6 alkyl, C r C 6 haloalkyl, C 2 -C 6 alkoxyalkyl, C 3 -C 6 alkenyl, O / \ C 3 -C 6 alk nji and CH 2 CH-CH 2 . R 4 is H, C j -C 3 alkyl and halogen; R 5 is H, halogen, C C3 alkyl, C1-C3 haloalkyl, cyclopropyl, vinyl, C 2 alkynyl, CN, C(O)R 6 , C(O) 2 R 6 , C(O)NR6R7, CR R9CN, CR8R9C(O)R6, CR 8 R9C(0) 2 R6, CR 8 R 9 C(O)NR6R7 > CHR β OH, CHR 8 OC(O)R 6 and OCHR OC(O)NR6R7 ; R 6 and R 7 are independently H and C1-C4 alkyl; R 8 and R? are independendy H and C1-C4 alkyl; W is O and S; Z is CH 2 and O; m is 1-5; and n is 1-3; when m or n are greater than 1, R 1 may be the same or independendy selected from the defined substituents; which involves the following reactions: first, reacting compounds of Formula V ,NHCΌ 2 R 2 wherein R 2 is Cj-Cg alkyl; with an anhydrous acid to produce compounds of Formula IN CO^ wherein X is Cl or Br and R 2 is described above; second, reacting compounds of Formula IN with Formula HI hydrazines or salts thereof Q— NHΝH 2 m wherein Q is defined above; to produce compounds of Formula II π wherein R 2 is defined above; and third, heating compounds of Formula II in liquid form optionally in the presence of an acid to produce Formula I compounds at 0-150°C with or without a solvent wherein Q and Z are defined above. This invention further pertains to novel Formulae II and IN intermediates π iv wherein Q, R 2 , and X are defined above. In the above definitions, the term "alkyl", used either alone or in compound words such as "alkylthio" or "haloa-kyl", includes straight chain or branched alkyl, such as methyl, ethyl, Λ-propyl, isopropyl and the different butyl, pentyl, and hexyl isomers. "Alkoxy" used either alone or in compound words such as "haloalkoxy" includes methoxy, ethoxy, n-prσpoxy, isopropoxy, and the different butoxy, pentoxy, and hexyloxy isomers. "Alkenyl" used either alone or in compound words such as "haloalkenyl" or "alkenylthio" includes straight chain or branched alkenes, such as vinyl, 1-propenyl, 2-propenyl, 3-propenyl and the different butenyl, pentenyl, and hexenyl isomers. "Alkynyl" used either alone or in compound words such as "haloalkynyl" or "alkynylthio" includes straight or branched alkynes, such as 1-propynyl, 3-propynyl, and die different butynyl, pentynyl, and hexynyl isomers. "Alkylthio" includes methylthio, ethylthio, and the different propylthio, butylthio, pentylthio, and hexylthio isomers. The term "halogen", used either alone or in compound words such as "haloalkyl", means fluorine, chlorine, bromine or iodine. Further, when used in compound words such as "haloalkyl" said alkyl can be partially or fully substituted with halogen atoms, which can be the same or different. Examples of haloalkyl include CF 3 , CH 2 CH 2 F, CF 2 CF 3 , CH 2 CHFC1, and CHBrCH 3 . The terms "haloalkenyl" and "haloalkynyl" are defined analogously to the term "haloalkyl". The total number of carbon atoms in a substituent group is indicated by the "C j -Cj" prefix where i and j are numbers from 1 to 8. For example, C3 alkynyloxy designates OCH 2 C≡CH, and C 4 alkynyloxy includes OCH 2 C≡CCH 3 , OCH 2 CH 2 G≡CH and OCH(CH 3 )C≡CH; C 2 alkylcarbonyl designates C(O)CH 3 , and C 4 alkylcarbonyl includes C(O)CH 2 CH 2 CH 3 and C(O)CH(CH 3 ) 2 ; C 2 alkoxy carbonyl designates C(O) CH3, and C 4 alkoxycarbonyl includes C(O) 2 CH 2 CH 2 CH 3 and C(O) 2 CH(CH 3 ) 2 ; C 3 alkylcarbonylalkoxy designates OCH 2 C(O)CH 3 , and C 4 alkylcarbonylalkoxy includes OCH 2 C(O)CH 2 CH 3 , OCH(CH 3 )C(O)CH 3 , and OCH 2 CH 2 C(O)CH 3 ; C 3 alkoxycarbonylalkoxy designates OCH 2 C(O) 2 CH3, and C 4 alkoxycarbonylalkoxy includes OCH 2 C(O) 2 CH 2 CH 3 , OCH(CH 3 )C(O) 2 CH 3 , and OCH 2 CH 2 C(O) 2 CH 3 ; C 3 alkylcarbonylalkylthio designates SCH 2 C(O)CH 3 , and C alkylcarbonylalkylthio includes SCH 2 C(O)CH 2 CH 3 , SCH(CH 3 )C(O)CH 3 , and SCH 2 CH 2 C(O)CH3; and as a final example C3 alkoxycarbonylalkylthio designates SCH C(O) 2 CH 3 , and C alkoxycarbonylalkylthio includes SCH 2 C(O) 2 CH 2 CH 3 , SCH(CH 3 )C(O) 2 CH 3 , and SCH 2 CH 2 C(O) 2 CH 3 . When a compound is substituted with a substituent bearing a subscript that indicates the number of said substituents can exceed 1, said substituents (when they exceed 1) are independendy selected from the group of defined substituents. Specifically preferred processes for die greatest utility of their products are: A) The process to prepare Formula I compounds wherein Q is Q- 1. B) The process of Preferred A to prepare Formula I compounds selected from the group: 2-[2,4-dichloro-5-(2-propynyloxy phenyl]-5,6,7,8-tetrahydro- l,2,4-triazolo[4,3-a]pyridin-3(2H)-one; ethyl [[2-cWoro-4-fluoro-5-(5,6,7,8-tetrahydro-3-oxo-l,2,4- triazolo[4,3-a]pyridin-2(3H)-yl)phenyl]thio]acetate; and 2-(2,4-dichloro-5-hydroxyphenyl)-5,6,7,8-tetrahydro-l,2,4- triazolo[4,3-a]pyridin-3(2H)-one. C) The process to prepare Formula I compounds wherein Q is Q-2. D) The process of Preferred C to prepare the Formula I compound: 2-(5,7-dicWoro-2,3-dmydro-2-me l-4-berιzofuranyl)-5,6,7,8- tetrahydro- 1 ,2,4-triazolo[4,3-a]-pyridin-3(2H)-one. E) The process to prepare Formula I compounds wherein Q is Q-3. F) The process to prepare Formula I compounds wherein Q is Q-4. G) The process of Preferred F to prepare the Formula I compound: 6-(5,6,7,8-tetrahydro-3-oxo-l,2,4-triazolo[4,3-a]pyridin-2(3H)- yl)-4-(2-propynyl)-2H-l,4-benzoxazin-3(4H)-one. Compounds produced by the process of the invention are active herbicides for selective and/or general broadleaf and grass weeds control in all plantation crops which include coffee, cocoa, oil palm, rubber, sugar cane, citrus, grapes, fruit trees, nut trees, banana, plantain, pineapple, conifers, e.g., loblolly pine, and turf species Kentucky bluegrass, St. Augustine grass, Kentucky fescue and bermudagrass. The intermediates of die present invention are useful as such in die process of the invention to produce die active herbicides. DETAILED DESCRIPTION OF THE INVENTION The first stage (a) of the process (Scheme I) is as a rule carried out by contacting one or more equivalents of an anhydrous hydrogen halide, preferably 2 to 2.5 equivalents of hydrogen chloride, at a temperature between -40°C and 40°C, preferably at 5-15°C, with a compound of Formula V, preferably die methyl carbamate, either in an inert hydrocarbon, chlorinated hydrocarbon, or ethereal solvent, preferably toluene, with or without solvent. The solvent is advantageously used in an amount from 100 to 2000 percent by weight, based on starting material V, and die reaction may be conducted at atmospheric or superatmospheric pressure in either a continuous or a batchwise mode. The products of Formula IV are generally isolated by removal of excess hydrogen halide under reduced pressure followed by removal of solvent or filtration and washing with a suitable oxygenated solvent such as tetrahydrofuran. Alternatively, they may be used widiout purification following the purge of excess hydrogen halide. Carbamates of Formula V are either known or can be prepared by various methods known to one skilled in die art. For example, Synthesis, (1984) 831 describes die preparation of Formula V carbamates by amidomercuration-reductive alkylation of alkenes and amides. Scheme I rv wherein R 2 , X, and Z are as described previously. The second stage (b) of the process, illustrated in Scheme II, is as a rule carried out by contacting the hydrohalide salt of Formula IN with an approximately equivalent molar amount of a hydrazine compound of Formula HI or a salt thereof and a sufficient amount of acid binding agent to maintain an effective pH of 3.5 to 7.0, preferably at 4.5 to 5.5, in a suitable non-reactive solvent, preferably, but not limited to, acetonitrile or alcohols such as methanol, at a temperature between -40 and 80°C, preferably at -20°C to 30°C. The acid-binding agent used may be any weakly-basic anhydrous material but is preferably a weak tertiary amine base such as pyridine or an alkali metal carboxylic acid salt such as sodium acetate, and is preferably used in amounts of between 0.5 to 1.5 equivalents, based on the total amount of acid bound in the compounds of Formulae HI and JN. Hydrazines of Formula in are either known or can be prepared by various methods known to one skilled in die art. For example, U.S. 4,881,967 and references cited therein, describe the preparation of hydrazines by diazotization of appropriately substituted amines known in die art. Scheme π Stage (b) wherein Q is as described previously. Preparation of Formula I compounds (Stage (c)) is as a rule carried out by allowing a compound of Formula II to react, optionally widi a solvent, at a temperature between 0 and 150°C, advantageously in the presence of an acidic catalyst, eidier at atmospheric, subatmospheric, or superatmospheric pressures (Scheme HI). A wide range of solvents may be used, but are preferably non-ketonic, neutral or only weakly acidic. Especially preferred are toluene. acetone, etiryl acetate, and isopropyl acetate, preferably used in amounts of between 100 and 2000 percent. The reaction is optionally acid-catalyzed, and 0.01 to 100 molar equivalents of formic, acetic, propionic acid and die like may be used, preferably using 0.1 to 3 equivalents, preferably operating the process at temperatures from 25-100°C. The end product of the process, a compound of Formula I, is then isolated by cooling die reaction mixture, optionally adding a non-polar solvent, such as hexanes, and filtering the precipitated product. Scheme HI Stage (c) π Alternatively, Formula I compounds may be prepared by heating die reaction mixture of Stage (b) from 25-150°C, but is preferably carried out by first isolating die intermediate compounds of Formula II and conducting ie reaction as described for Stage (c). EXAMPLE 1 Step A: Preparation of methyl 2-imino-l-piperidinecarboxylate hydrochloride Bromine (6.5 kg) is added subsurface to a solution of 5.1 kg of 5-cyano- valeramide and 4.45 kg of sodium methylate in 27.5 kg of medianol at 0-5 °C. The resulting mixture is transferred slowly to 24 kg of hot (60 °C) medianol to maintain die temperature at 50-65 °C. The majority of the methanol is removed by distillation, toluene (30 kg) is added, and die distillation is continued until all of d e medianol is removed. The mixture is then filtered to obtain an approximately 18% (wt/wt) solution of methyl 4-cyanobutyl carbamate in toluene. A portion of tiiis solution (259 g) is maintained at 15-20°C while 33 g of anhydrous hydrogen chloride is bubbled in during two hours. The two-phase mixture is then purged of excess HC1 at 150 torr and 100 mL of tetrahydrofuran is added. The product is filtered and washed witii tetrahydrofuran to remove residual HC1. The tide compound is us obtained as 53 g (95%) of a white crystalline solid, m.p. 118-119 °C (dec). *H NMR (CDC1 3 ) δ 1.7 (t, 2H), 1.8 (t, 2H), 3.15 (t. 2H ). 3.8 (t, 2H), 3.82 (s, 3H), 10.2 (br s, IH), 12.75 (br s, IH). Step B: Preparation of mediyl 2-rr2.4-dicrrioro-5-(2-propynyloxy)phenyl1- hydrazonol- 1 -piperidinecarboxylate To a mixture of 12.3 g of anhydrous sodium acetate and 80 mL of acetonitrile is added 13.3 g of 91% 2,4-dichloro-5-(propargyloxy)phenyl-hydrazine hydrochloride and, after 30 minutes of vigorous stirring, the mixture is cooled to 0-5 °C. before adding 10.0 g of the product from Step A. The mixture is stirred vigorously for lh at 5-10 °C and is then poured into 200 mL of cold water. The product is filtered, washed witii 30 mL of cold water and dien witii 30 mL of cold isopropanol, and dried to provide 16.0 g (95%) of die tide compound as a solid, m.p. 137-138 °C. H NMR (CDC1 3 ) δ 1.74 (m, 2H), 1.82 (m, 2H), 2.46 (t, 2H, J=6Hz), 2.52 (d, IH, J=2.4Hz), 3.68 (t, 2H, J=6Hz), 3.73 (s, 3H), 4.75 (d, 2H, J=2.4Hz), 7.13 (s, IH), 7.23 (s, IH), 7.26 (br s, IH). Step C: Preparation of 2-f2.4-dichloro-5-(2-propynyloxy)phenyn-5.6.7.8- tetrahydro-1.2.4-triazolor4.3-a]-pyridin-3(2H)-one A mixture of 10.0 g of the product from Step B and 0.50 g of glacial acetic acid in 50 mL of toluene is heated at 100 °C for 2 h while removing methanol vapor witii a stream of nitrogen. Hexane (50 mL) is added at 70 °C and die product is filtered at 25 °C and washed with hexanes to provide 8.0 g (94%) of die title compound, m.p. 168-169 °C. l H NMR (CDC1 3 ) δ 1.9 (m, 4H), 2.55 (t, IH, J=2.4Hz), 2.74 (t, 2H, J=6Hz), 3.67 (t, 2H, J=6Hz), 4.74 (d, 2H, J=2.4Hz), 7.13 (s, IH), 7.50 (s, IH). EXAMPLE 2 Step A: Preparation of methyl 2-f2.4-dichloro-5-hydroxyphenyl)hydrazono1- 1 -piperidinecarboxylate A mixture of 18.5 g of sodium acetate and 320 mL of dry medianol is cooled to -20 °C and 28.8 g of the product from Example 1, Step A is added, followed by 34.8 g of 96% pure 2,4-dichloro-5-hydrazinophenol hydrochloride. The mixture is stirred for lh at -10 to 0 °C and tiien is poured into 500 mL of ice water. The product is filtered, washed witii tiiree 100 mL portions of water and dried in vacuo to provide 44.6 g of die title compoimd as an orange solid, m.p. 158-159 °C. H NMR (DMSO-d 6 ) δ 1.7 (m, 4H), 2.5 (t, 2H, J=5.4Hz), 3.57 (t, 2H, J=5.4Hz). 3.64 (s, 3H), 7.00 (s, IH), 7.25 (s, IH), 8.15 (br s, IH), 10.3 (br s, IH). Step B: Preparation of 2-(2.4-dichloro-5-hydroxyphenyl)-5.6.7.8-tetrahydro- L2.4-triazolor4.3-a1pyridin-3(2H)-one A mixture of 50 g of the product from Step A and 100 mL of a 5% solution of acetic acid in toluene is heated at 65-70 °C for 3 h witii removal of methanol by a stream of nitrogen. Hexanes (50 mL) is then added and die mixture is filtered at ambient temperature, washed sequentially with 50 mL of hexanes and two 50-mL portions of cold isopropanol, and dried to provide 37 g of die title compound, m.p. 214-216 °C (218-219 °C recrystallized from aq. EtOH). l H NMR (DMSO-d 6 ) δ 1.8 (m, 4H), 2.6 (t, 2H, J=6Hz), 3.50 (t, 2H, J=6Hz), 7.09 (s, IH), 10.9 (br s, IH).

Claims: What is claimed is: 1. A process for preparing compounds of the Formula IV 2 wherein X is Cl or Br, R 2 is C r C 6 alkyl, and Z is CH or O comprising reacting a compound of Formula V _,NHOW wherein R 2 and Z are as described above: widi an anhydrous acid at -40 to 40°C. 2. The process of Claim 1 wherein the compounds of Formula IV are reacted witii hydrazines of die Formula HI or salts thereof Q— NHNH 2 m in the presence of a suitable solvent and an anhydrous binding agent at -40° to 80°C to produce compounds of Formula H II wherein Q is Q-3 CM R 1 is H, halogen, OH, C r C 6 alkyl, C r C 6 haloalkyl, C r C 6 alkoxy, C r C 6 haloalkoxy, Cj-Cg alkylthio, Cj-Cg haloalkylthio, C -Cβ alkenyloxy, C 2 -C 6 alkenyldiio, C 2 -Cg haloalkenyloxy, C 2 -Cg haloalkenylthio, C3-C6 alkynyloxy, C3-C6 alkynylthio, C3-C6 haloalkynyloxy, C3-C6 haloalkynylthio, C 2 -C6 alkylcarbonyl, C 2 -C6 alkoxycarbonyl, C 4 -Cg alkenyloxycarbonyl, C3-C8 alkylcarbonylalkoxy, C3-C8 alkylcarbonylalkylthio, C3-C8 alkoxycarbonylalkoxy, C3-C8 alkoxycarbonylalkyldiio, C5-C8 alkenyloxycarbonylalkoxy, C5-C8 alkenyloxycarbonylalkylthio, phenoxy and phenyltiiio where die phenyl groups are optionally substituted with halogen; R 2 is C r C 6 alkyl; R 3 is H, C r C 6 alkyl, C r C 6 haloalkyl, C 2 -C 6 alkoxyalkyl, C 3 -C 6 alkenyl. O / \ C 3 -C 6 alkynyl and CH 2 CH-CH 2 ; R 4 is H, C r C 3 alkyl and halogen; R 5 is H, halogen, C!-C 3 alkyl, 0^3 haloalkyl, cyclopropyl, vinyl, C 2 alkynyl, CN, C(O)R 6 , C(O) 2 R 6 , C(O)NR 6 R 7 , CR 8 R 9 CN, CR 8 R9C(O)R 6 , CR 8 R 9 C(O) 2 R 6 , CR 8 R 9 C(O)NR 6 R 7 , CHR 8 OH, CHR 8 OC(O)R 6 and OCHR 8 OC(O)NR 6 R 7 ; R 6 and R 7 are independendy H and C C alkyl; R 8 and R 9 are independendy H and CJ- J alkyl; W is O and S; Z is CH 2 and O; m is 1-5; and n is 1-3; when m or n are greater than 1, R 1 may be the same or independendy selected from the defined substituents. 3. The process of Claim 2 wherein the compounds of Formula II are heated at 0 to 150°C optionally in die presence of a solvent and an acid catalyst to produce compounds of Formula I 4. The process of Qaim 3 wherein Q is Q- 1. 5. The process of Qaim 4 wherein the Formula I compound is selected from die group: 2-[2,4-dichloro-5-(2-propynyloxy)phenyl]-5,6,7,8-tetrahydro-l,2,4- triazolo[4,3-a]pyridin-3(2H)-one; ediyl [[2-chloro-4-fluoro-5-(5,6,7,8-tetrahydro-3-oxo-l,2,4-triazolo[4,3- a]pyridin-2(3H)-yl)phenyl]dιio]acetate; and 2-(2,4-dichloro-5-hydroxyphenyl)-5,6,7,8-tetrahydro-l ,2,4-triazolo[4,3- a]pyridin-3(2H)-one. 6. The process of Qaim 3 wherein Q is Q-2. 7. The process of Qaim 6 wherein the Formula I compound is 2-(5,7-dichloro-2,3-dihydro-2-methyl-4-benzofuranyl)-5,6,7,8-tetrahydro- 1 ,2,4-triazolo[4,3-a]-pyridin-3(2H)-one. 8. The process of Claim 3 wherein Q is Q-3. 9. The process of Claim 3 wherein Q is Q-4. 10. The process of Claim 9 wherein the Formula I compound is 6-(5,6,7,8-tetrahydro-3-oxo-l,2,4-triazolo[4,3-a]pyridin-2(3H)-yl)-4-(2- propynyl)-2H- 1 ,4-benzoxazin-3(4H)-one. 11. Compounds of the Formula II and IV wherein Q is Q-3 CM R 1 is H, halogen, OH, C r C 6 alkyl, C r C 6 haloalkyl, C r C 6 alkoxy, C r C 6 haloalkoxy, C j -Cg alkylthio, Cj-Cg haloalkylthio, C 2 -Cg alkenyloxy, C 2 -C 6 alkenyldiio, C 2 -Cg haloalkenyloxy, C 2 -Cg haloalkenylthio, C -C6 alkynyloxy. C3-C6 alkynylthio, C3-C haloalkynyloxy, C3-C6 haloalkynyluiio. C 2 -C 6 alkylcarbonyl, C 2 -Cg alkoxycarbonyl, C -Cg alkenyloxycarbonyl, C3-C8 alkylcarbonylalkoxy, C3-C8 alkylcarbonylalkyldiio, C3-C8 alkoxycarbonylalkoxy, C3-C8 alkoxycarbonylalkylthio, C 5 -C 8 alkenyloxycarbonylalkoxy, C5-C alkenyloxycarbonylalkyldiio, phenoxy and phenylthio where the phenyl groups are optionally substituted with halogen; R 2 is C r C 6 alkyl; R 3 is H, C r C 6 alkyl, C r C 6 haloalkyl, C 2 -C 6 alkoxyalkyl, C 3 -C 6 alkenyl, O / \ C 3 ~ C 6 a^^y 1 and CH 2 CH- CH 2 ; R 4 is H, C r C 3 alkyl and halogen; R 5 is H, halogen, C1-C3 alkyl, C1-C3 haloalkyl, cyclopropyl, vinyl, C 2 alkynyl, CN, C(O)R 6 , C(O) 2 R 6 , C(O)NR6R 7 , CR 8 R9CN, CR 8 R9C(O)R 6 , CR 8 R9C(O) 2 R 6 , CR 8 R9C(O)NR 6 R 7 , CHR OH, CHR 8 OC(O)R 6 and OCHR 8 OC(O)NR 6 R 7 ; R 6 and R 7 are independendy H and C j - alkyl; R 8 and R are independendy H and Cι~C 4 alkyl; W is O and S; X is Cl andBr; Z is CH 2 and O; m is 1-5; and n is 1-3; when m or n are greater than 1, R 1 may be the same or independendy selected from me defined substituents.

Inventors: SHAPIRO RAFAEL, SHAPIRO, RAFAEL
Applicants: DU PONT, SHAPIRO RAFAEL, E.I. DU PONT DE NEMOURS AND COMPANY, SHAPIRO, RAFAEL
Application year: 1994
Main classification: C07D211
IPC codes: A01N43, C07D211, C07D265, C07D405, C07D413, C07D417, C07D471, C07D498